5α-reductase inhibitors, such as finasteride and dutasteride, are used to treat benign prostatic hyperplasia (BPH), a common condition that can lead to urinary retention (inability to voluntarily urinate). These drugs reduce prostate size, the risk of acute urinary retention and need for surgical intervention in men with BPH. 5α-reductase inhibitors are used to treat chronic urinary retention as the onset of action is slow; treatment for at least six months may be necessary to assess whether a beneficial response has been achieved. Thereafter, treatment should be continued long term. Dutasteride is available as a combination product with tamsulosin; an alpha1-adrenoceptor blocker, which is another option to treat urinary retention. The following article will describe the mechanism of action, cautions and contraindications, side effects and clinically significant interactions for 5α-reductase inhibitors. Mechanism of Action In BPH, enlargement of the prostate gland is dependent upon the conversion of testosterone to more potent androgen dihydrotestosterone (DHT) within the prostate. DHT is a potent male sex hormone that can cause the prostate to grow, which has greater affinity than testosterone for androgen receptors. Interestingly, topical finasteride is also used to treat male pattern baldness, commonly alongside minoxidil, as DHT is responsible for hair follicle shrinkage. 5α-reductase inhibitors block the enzyme 5α-reductase, preventing this conversion and leading to a reduction in prostate volume over time. Drug Enzyme Inhibition Profile Finasteride Selective, competitive inhibitor of Type II 5α-reductase Dutasteride Inhibits Type I and Type II 5α-reductase isoenzymes Created in BioRender. Boucher, M. (2025) https://BioRender.com/afmd9nk Fig 1: 5α reductase inhibitors: mechanism of action Pharmacokinetics The pharmacokinetics of finasteride and dutasteride are described below: Parameter Finasteride Dutasteride Formulation Standard-release tablet Standard-release capsule Bioavailability (F) ~80% ~60% Tmax ~2 hours 1–3 hours Metabolism Primarily via CYP3A4 but no clinically significant drug interactions Primarily via CYP3A4 and CYP3A5 Elimination route Urine and faeces Mainly hepatic; minimal renal excretion Half-life 5-6 hours 3–5 weeks Effect of hepatic impairment No data available ↑ Plasma levels and prolonged half-life – use with caution Effect of renal impairment No adjustment required as faecal excretion increases commensurate to the decrease in urinary excretion of metabolites No clinically significant accumulation Contraindications Finasteride is contraindicated in pregnancy (including handling tablets) as exposure may cause abnormalities of the external genitalia of a male foetus when administered to a pregnant woman. Furthermore, dutasteride is contraindicated in women and children (including handling tablets as dutasteride is absorbed through the skin). Dutasteride is also contraindicated in severe hepatic impairment as this is the main route of elimination. Cautions PSA is a protein produced by normal cells in the prostate and also by prostate cancer cells. PSA levels are often raised in prostate cancer and in enlarged prostate (as patients get older and the prostate gets larger). Decreases in prostate specific antigen (PSA) concentrations have been reported by approximately 50% in patients with BPH during treatment with 5-alpha-reductase inhibitors, even in the presence of prostate cancer. This effect occurs within the first months of therapy, after which time PSA levels stabilise to a new baseline In patients treated with finasteride or dutasteride for six months or more, PSA values should be doubled for comparison with normal ranges in untreated men Total serum PSA levels return to baseline within 6 months of discontinuing treatment Cases of male breast cancer have been reported in patients treated with finasteride and dutasteride, and patients should be advised to report any breast changes such as lumps, pain, or nipple discharge. Furthermore, psychiatric adverse effects, including depression and suicidal ideation, have also been associated with this class and warrant careful monitoring. Dutasteride should be used cautiously in patients with mild to moderate hepatic impairment due to hepatic metabolism. Additionally, an increased incidence of cardiac failure has been observed with combination therapy involving dutasteride and tamsulosin, and this potential risk should be considered when initiating treatment. Adverse Effects Adverse effects include gynaecomastia, decreased libido and psychological effects such as depression, anxiety and suicidal thoughts. Interactions Long-term coadministration with potent CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, clarithromycin) with dutasteride may increase plasma levels and prolong half-life. Reduction in dosing frequency can be considered an option to minimise adverse effects. Finasteride has no found clinically significant drug interactions. References https://www.medicines.org.uk/emc/product/547/smpc#gref https://www.medicines.org.uk/emc/product/8988/smpc#gref Ritter JM, Flower RJ, Henderson G, Loke YK, MacEwan DJ. Rang & Dale’s Pharmacology. 9th ed. London: Elsevier; 2019. Do you think you’re ready? 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